We are in the process of developing F-18 (110 min) labeled biotin derivatives to be used for the in vivo labeling of interleukin-2 receptor monoclonal antibodies (MAbs) covalently linked to streptavidin. The strategy is to use a multi-step paradigm that involves first the injection of unlabeled streptavidin-conjugated MAb. Next, after sufficient time to allow for the conjugates's uptake into target tissues and its clearance from nontarget tissues, a second injection of F-18 labeled biotin is given, and the smaller, more easily diffusible F-18 labeled biotin molecule is used to selectively label the MAb. Two different biotin derivatives have been prepared thus far, each showed dramatic differences in serum stability. N1-(4- [18F]fluoromethylphenylcarboxamido)-N2-biotinyl ethylene diamine, 4- (4-(2-(4-[18F]fluoromethylphenylcarboxamido)ethylcarbamoyl)butyl)-2- oxoperhydrothieno- [3,4-d]imidazole had a serum half-life of less than 25 minutes, whereas N6-(4-[18F]fluoromethyl phenylcarboxamido)N2-biotinyl lysine, 6-(4-[ 18F]fluoromethylphenylcarboxamido)-2-(4-(2-oxoperhydrothieno[3,4-d]- imidazol-4-yl)butylcarboxamido)hexanoic acid showed no decomposition even after 90 minutes. We will be evaluating the in vivo binding of these biotin derivatives to strepavidin-conjugated IgG as well as uptake and clearance in the presence of conjugate. These findings will be applied to IL2-specific MAb streptavidin conjugate.